In order to obviate large and rapid perturbations of arterial blood gas and acid-base status, the body must be capable of clearing the additional CO2 delivered to the lungs under those conditions in which cardiac output and/or mixed venous CO2 increase. Under such conditions ventilation normally does increase rapidly in proportion to the CO2-flux to the lungs, with consequent regulation of arterial PCO2 and pH. Thus, a highly sensitive ventilatory control system exists which mediates an isocapnic hyperpnea both in the steady-state and transient-state of the perturbations. However, current concepts of respiratory control physiology are totally inadequate to describe this important feature of ventilatory control. We plan to elucidate the mechanisms of this control process, utilizing computer techniques to determine carefully, the ventilatory, gas exchange (both breath-by-breath) and blood gas response kinetics in response to several modes of modifying CO2-flux to the lungs, such as: a) exercise; b) cardiac output variations; c) venous CO2 loading and unloading; d) redistribution of pulmonary blood flow; and, e) various combinations of the above. The experiments (in dogs) will be repeated following bilateral carotid body resection and/or cervical vagotomy. We hope to characterize the proportional role of the rapidly responding CO2 chemoreceptors in the isocapnic hyperpnea with special reference to the temporal characteristics.